Prediction of severe ovarian hyperstimulation syndrome in women undergoing in vitro fertilization using day 3 estradiol levels, collected ova, and the number of follicles

Abstract

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening iatrogenic condition that can occur during in vitro fertilization (IVF). The worst outcome is hydrothorax, hypovolemia, higher risk of deep venous thrombosis and oliguria. With severe OHSS patients are required to postpone embryo transfer for an undetermined amount of time. Predicting which patients are a high risk of developing OHSS is mainly based on serum estradiol (E2) levels, but other factors, such as female age, BMI, ovarian volume, antral follicle count (AFC), and polycystic ovary syndrome, are speculated to be predictive. Here, we aimed to determine if E2 levels at Day 3 and its fold change at day ten as well as antral follicle count and ova collected are predictive factors for severe OHSS. Retrospective case-control study. Patient chart review was performed between January 2008 and December 2017 at Ingenes in Mexico City. Three hundred twenty-seven women were selected. E2 >3000 ng/L usually on the last day of stimulation (day 10 with three 18 mm-follicles) was defined as OHSS (n=151). Culdocentesis was performed on a patient when upon clinical assessment patient presented features such as nausea, vomiting, oral intolerance and ascites identified by endovaginal ultrasound and abdominal ultrasound (renal and hepatic areas with visible ascites) that do not respond to conservative management (n=55 severe OHSS). Predictability was evaluated by measuring the area under the receiver-operating characteristic (AUC). Differences between groups were determined by t-test. The OHSS positive group, when compared to the non-OHSS group, was higher with respect to E2 Day 3 levels (150±230 v 250±177 ng/L), E2 fold change (20.1±23.8 v 32.2±29.1), AFC (11.6±8.3 v 18.2±9.1), and Ova collected (10.1±6.4, 21.1±9.0, p<0.001). E2 Day 3 levels (AUC=0.76, 95%CI: 0.71-0.82), E2 fold change (AUC=0.71, 95%CI: 0.65-0.77), AFC (AUC=0.75, 95%CI: 0.70-0.81), and Ova collected (AUC=0.85, 95%CI: 0.81-0.89) were predictive of OHSS. For Culdocentesis, E2 Day 3 levels (190±221 v 232±158 ng/L) were not different between the subjects who received culdocentesis, whereas the E2 fold change (24.5±26.6 v 32.9±28.8, p=0.038), AFC (13.7±9.0 v 19.8±8.9, p<0.001), and Ova collected (13.7±8.9, 23.3±8.1, p<0.001) were higher. Interestingly, all variables were predictive of subjects who would qualify for culdocentesis (E2 Day 3 levels: AUC=0.63, 95%CI: 0.55-0.70; E2 fold change: AUC=0.63, 95%CI: 0.55-0.71; AFC: AUC=0.74, 95%CI: 0.68-0.80; and Ova collected: AUC=0.80, 95%CI: 0.75-0.85). Here, we demonstrate the E2 levels, as well as the ova production parameters, are indicators of IVF patients who could develop severe OHSS and may require culdocentesis.